A regulação endócrina dos balanços de cálcio

RESUMO: As concentrações circulantes de cálcio são notavelmente constantes a despeito das variações diárias na absorção intestinal e na eliminação renal deste elemento. A regulação da calcémia é um sistema complexo que compreende vários factores controladores (a calcémia, a fosforémia, as concentrações circulantes de paratormona (PTH) e calcitriol além de muitos outros factores como hormonas esteróides em geral, outros iões como o magnésio e outros factores hormonais) e vários órgãos alvo (glândulas paratiroideias, osso, rim e intestino). As respostas dos órgãos alvo também são muito variadas. No caso mais simples, a cristalização de sais de cálcio corresponde a uma mudança de fase em que participam moléculas orgânicas que a iniciam, aceleram ou inibem. Em geral a combinação de um factor controlador com o respectivo receptor de membrana (para polipeptídeos ou iões) ou intracelular (hormonas esteróides) é apenas o primeiro passo de uma cadeia bioquímica que introduz uma enorme amplificação na resposta. A esta variedade de mecanismos de resposta correspondem grandes diferenças nos tempos de resposta que podem ser de minutos a semanas. É hoje possível “observar” (medir) com apreciável rigor nos líquidos biológicos (sangue, urina, fezes, etc.) os factores mais importantes do sistema de regulação da calcémia (cálcio, fósforo, paratormona e calcitriol) assim como administrar estes factores em experiências agudas. Esta possibilidade reflecte – se na literatura neste campo que tem vindo a crescer. O advento das técnicas da biologia molecular tem permitido a caracterização molecular de algumas das disfunções da homeostase do cálcio e é de esperar um diagnóstico fisiopatológico cada vez mais rigoroso dessas disfunções. Com o avanço dos conhecimentos nesta área que não cessa de aumentar temos cada vez maiores capacidades para fazer diagnósticos e é cada vez mais difícil interpretar com rigor os correspondentes quadros metabólicos. A análise ou síntese de sistemas complexos é a actividade mais nobre dos engenheiros que lhes permite desenhar pontes, diques, barcos, aviões ou automóveis. Com o aparecimento de computadores de médio ou grande porte foi – lhes possível utilizar descrições matemáticas não só para desenhar sistemas como ainda para interpretar eventuais falhas na sua operação. Essas descrições matemáticas consistem numa sequência de operações realizadas num computador segundo um “programa informático” que receberam a designação genérica de modelos, por analogia com as famosas leis (equações) da física que foram deduzidas a partir de um certo número de postulados e que permitem representar matematicamente processos físicos. As famosas leis de Newton são talvez os exemplos mais famosos de “modelos” de sistemas físicos. A introdução de modelos matemáticos em biologia e particularmente em medicina só se deu recentemente.MÉTODOS No trabalho que aqui se apresenta construiu - se um modelo simplificado da homeostase do cálcio destinado ao cálculo de variáveis observáveis (concentrações de cálcio, fósforo, PTH e calcitriol) de modo a poderem comparar-se valores calculados com valores observados. A escolha dos componentes do modelo foi determinada pela nossa experiência clínica e pela informação fisiopatológica e clínica publicada. Houve a preocupação de construir o modelo de forma modular de modo a ser possível a sua expansão sem grandes transformações na descrição matemática (e informática) já existente. Na sua fase actual o modelo não pode ser usado como instrumento de diagnóstico. É antes uma ferramenta destinada a esclarecer “em princípio” mecanismos fisiopatológicos. Usou – se o modelo para simular um certo número de observações publicadas e para exemplificar a sua eventual aplicação clínica na simulação de situações hipotéticas e na análise de possíveis mecanismos fisiopatológicos responsáveis por situações de hipo ou hipercalcémias. Simultaneamente fez – se uma análise dos dados acumulados relativos a doentes vistos no Serviço de Endocrinologia do Instituto Português de Oncologia de Francisco Gentil – Centro Regional Oncológico de Lisboa, S.A. CONCLUSÕES Numa população de 894 doentes com patologias variadas do Instituto Português de Oncologia de Lisboa os valores da calcémia tiveram uma distribuição normal unimodal com uma média de 9.56 mg/dl, e um erro padrão de 0.41 mg/dl. Estas observações sugerem que a calcémia está sujeita a regulação. A partir dos resultados publicados em que o metabolismo do cálcio foi perturbado por infusões de cálcio, calcitriol ou PTH, de estudos bioquímicos e fisiológicos sobre os mecanismos de acção de factores controladores da calcémia e do estudo do comportamento de órgãos alvo (paratiroideias, intestino, osso e rim) foi possível construir um modelo matemático de parâmetros concentrados do sistema de regulação da calcémia. As expressões analíticas usadas foram baseadas na cinética enzimática de modo a que os seus parâmetros tivessem um significado físico ou fisiológico simples. O modelo revelou apreciável robustez e flexibilidade. É estável quando não perturbado e transita entre estados estacionários quando perturbado. Na sua forma actual gera simulações que reproduzem satisfatoriamente um número apreciável de dados experimentais colhidos em doentes. Isto não significa que possa ser usado como instrumento de diagnóstico aplicável a doentes individuais. O desenho do modelo comporta a adição posterior de novas relações quando surgirem situações para as quais se revele insuficiente. A utilização exaustiva do modelo permitiu explicitar aspectos do metabolismo do cálcio que ou não estão contidas na sua formulação actual – o aparecimento de hipertrofia ou de adenomas das paratiroideias e as alterações na estrutura óssea , a participação de outros factores controladores – magnésio, ou estão insuficientemente descritas – alterações do metabolismo do fósforo nos hipoparatiroidismos. A análise dos dados relativos aos doentes do Serviço de Endocrinologia do IPO permitiu o início da caracterização dos tipos de patologia que representam e de possíveis mecanismos fisiopatológicos subjacentes. Estas observações são o ponto de partida para análises futuras. São exemplos das relações encontradas: a distribuição dos doentes por dois grandes grupos conforme a calcémia é determinada pelas concentrações circulantes de PTH ou estas são determinadas pela calcémia; a distribuição sazonal das concentrações de Vit. D25. no sangue; a correlação negativa entre estas e as concentrações de PTH no sangue. Também foi possível extrair a cinética do controlo da PTH sobre a síntese de calcitriol. O estudo dos níveis circulantes de PTH no pós-operatório imediato de doentes paratiroidectomizados permitiu determinar as suas taxas de degradação metabólica. O modelo permitiu simular as relações Ca/PTH no sangue, Ca/Fracção excretada da carga tubular, Ca/P no sangue para valores normais ou altos de Ca. Foram feitas simulações de situações fisiopatológicas (em “doentes virtuais”): infusões crónicas de cálcio, PTH e calcitriol; alterações no comportamento de receptores. Estas simulações correspondem a experiências que não podem ser realizadas em humanos. São exemplos da utilização do modelo na exploração de possíveis mecanismos fisiopatológicos através da observação de resultados quantitativos inacessíveis à intuição. O modelo foi útil em duas fases do trabalho: Primeiro, durante a sua síntese implicou uma escolha criticamente selectiva de informação, sua análise quantitativa e processamento, uma explicitação rigorosa (analítica) das relações funcionais entre os controladores e as variáveis e da sua integração numa estrutura global; Segundo, a simulação de situações experimentais ou clínicas (dados do Serviço de Endocrinologia do IPO) em doentes obrigou a explicitar raciocínios fisiopatológicos habitualmente formulados em bases puramente intuitivas. Esta prática revelou comportamentos óbvios após as simulações – acção reduzida das infusões PTH (simulação de hiperparatiroidismos primários) enquanto não há inibição total da respectiva secreção, necessidade de aumento da massa secretora da paratiroideia nas insuficiências renais avançadas, etc. A síntese e utilização do modelo não implicaram uma preparação matemática avançada e foram possíveis mercê da disponibilidade de “software” interactivo especificamente desenhado para a simulação de sistemas dinâmicos em que os programas se escrevem em inglês usando a simbologia simples da álgebra elementar. A função nobre de modelos desta natureza é semelhante à dos modelos usados pelos físicos desde o século XVII: permitir explicações de carácter geral funcionando como uma ferramenta intelectual para manipulação de conceitos e para a realização de “experiências pensadas” (“thought experiments”) respeitando certos princípios físicos (princípios de conservação) que estabelecem as fronteiras da realidade. -------ABSTRACT: Calcium blood levels are remarkably constant despite great variations in calcium daily intake, intestinal absorption and renal excretion. The regulation of the calcium concentration in the blood is achieved by a complex system that includes several controller factors (mainly the serum levels of calcium, phosphorus, parathyroid hormone (PTH) and calcitriol but also of steroid hormones, ions such as magnesium and other hormonal factors) and several target organs (parathyroid glands, bone, kidney and intestine). The functional response to the controlling factors obeys a variety of kinetics. The precipitation of calcium salts is a simple phase transition in which organic molecules may provide nucleation centres or inhibit the process. The combination of a controller factor with its receptor located in the cell membrane (for peptides or ions) or in the nucleus (for steroid hormones) is only the first step of a biochemical chain that introduces a huge amplification in the response. To this great variability of response we have to add the times of response that vary from minutes to weeks. It is possible to “observe” (measure) with great accuracy in biological fluids (blood, urine, faeces, etc.) the most important factors intervening in the calcium regulation (calcium, phosphorus, PTH and calcitriol). The response of the system to acute infusions of the controlling factors has also been studied. Using molecular biology techniques it has been possible to characterize some calcium homeostasis dysfunctions and better physiopathological diagnosis are expected. With the increasingly new knowledge in this area we have better capacity to diagnose but it is harder to explain correctly the underlying metabolic mechanisms. The analysis or synthesis of complex systems is the noble activity of engineers that enables them to draw bridges, dams, boats, airplanes or cars. With the availability of medium-large frame computers it was possible to use mathematical descriptions not only to draw systems but also to explain flaws in its operations. These mathematical descriptions are generally known as models by analogy with the laws (equations) of physics that allow the mathematical description of physical processes. In practice it is not possible to find general solutions for the mathematical descriptions of complex systems but (numeric) computations for specific situations can be obtained with digital computers. The introduction of mathematical models in biology and particularly in medicine is a recent event. METHODS In this thesis a simplified model of calcium homeostasis was built that enables the computation of observable variables (concentrations of calcium, phosphorus, PTH and calcitriol) and allows the comparison between the simulation values and observed values. The choice of the model’s components was made according to our clinical experience and to the published clinical and physiopathological data. The model has a modular design that allows future expansions with minor alterations in its structure. In its present form the model cannot be used for diagnosis. It is a tool designed to enlighten physiopathological processes. To exemplify its possible clinical application in the simulation of hypothetical situations and in the analysis of possible mechanisms responsible for hypo or hypercalcemias the model was used to simulate a certain number of published observations. An analysis of clinical and laboratory data from the Endocrinology Department of the Portuguese Cancer Institute (I.P.O.F.G.-C.R.O.L.,S.A.) is also presented. CONCLUSIONS In a population of 188 patients without an identifiable disease of the calcium metabolism at the Portuguese Cancer Institute the calcemia levels had a unimodal distribution with an average of 9.56 mg/dL and a S.E.M of 0.41 mg/dL. This observation confirms that serum calcium is regulated. Using published data; in which calcium metabolism was disrupted by calcium, PTH or calcitriol infusions; from biochemical and physiological studies of the action of controller factors on the calcemia; in which the response of target organs (parathyroid glands, intestine, bone, kidney) was studied it was possible to build a mathematical model of concentrated parameters of the calcium homeostasis. Analytical expressions used were based on enzymatic kinetics. The model is flexible and robust. It is stable when not disturbed and changes between steady states when disturbed. In its present form it provides simulations that reproduce closely a number of experimental clinical data. This does not mean that it can be used as a diagnostic tool for individual patients. The exhaustive utilisation of the model revealed the need of future expansions to include aspects of the calcium metabolism not included in its present form –hypertrophy or adenomas of the parathyroid glands, bone structure changes, participation of other controller factors such as magnesium – or insufficiently described – phosphate metabolism in hypoparathyroidism. The analysis of the data collected from the I.P.O.’s Endocrinology Department allowed the initial characterization of the different pathologies represented and of their possible physiopathological mechanisms. These observations are a starting point for future analysis. As examples of the relations found were: the distribution of patients in two groups according to the dependency of calcium by PTH levels or PTH levels by calcium concentration; the seasonal distribution of the serum concentrations of D25; its negative correlation with PTH concentration. It was also possible to extract the kinetics of the control of the synthesis of calcitriol by PTH. The analysis of immediate post-surgical levels of PTH in parathyroidectomized patients allowed the determination of its metabolic clearance. The model also allowed the simulation of the relations between Ca/PTH in blood, serum Ca/Fraction of tubular load excreted and Ca/P in blood for normal and high values of calcium. Simulations were made of pathological situations (in “virtual patients”): chronic infusions of calcium, PTH and calcitriol; changes in the characteristics of receptors. These simulations are not possible in real persons. They are an example of the use of this model in exploring possible mechanisms of disease through the observation of quantitative results not accessible to simple intuition. This model was useful in two phases: Firstly, its construction required a careful choice of data, its quantitative analysis and processing, an analytical description of the relations between controller factors and variables and their integration in a global structure. Secondly, the simulation of experimental or clinical (I.P.O.’s Endocrinology Department) data implied testing physiopathological explanations that previously were based on intuition. The construction and utilisation of the model didn’t demand an advanced mathematical preparation since user-friendly interactive software was used. This software was specifically designed for the simulation of dynamic systems. The programs are written in English using elementary algebra symbols. The essential function of this type of models is identical to that of those used by physicists since the XVII century which describe quantitatively natural processes and are an intellectual tool for the manipulation of concepts and the performance of “thought experiments” based in certain physical principles (conservation principles) that are the frontiers of reality.------------------RESUMÉE: Les concentrations circulantes de calcium sont constantes même pendant des variations de l’absorption intestinale et de l’élimination rénale de cet élément. La régulation de la calcémie est un système complexe qui comprend plusieurs éléments contrôleurs (la calcémie, la phosphorémie, les concentrations circulantes de l’hormone parathyroïdienne (PTH) e du calcitriol et d’autres comme les hormones stéroïdes ou des ions comme le magnésium) et plusieurs organes (glandes parathyroïdiennes, l’os, le rein et l’intestin). Les réponses de ces organes sont variées. Dans le cas plus simple, la cristallisation des sels de calcium correspond à un changement de phase dans lequel y participent des molécules organiques que la débutent, l’accélèrent ou l’inhibent. Généralement la combinaison d’un élément contrôleur avec leur récepteur de membrane (pour les peptides ou les ions) ou intracellulaire (pour les hormones stéroïdes) n’est que le premier pas d’une chaîne biochimique qu’introduit une grande amplification de la réponse. A cette variété de réponses correspondent des grandes différences des temps de réponses qu’y vont des minuits a semaines. Il est possible « observer » (mesurer) dans les fluides biologiques (sang, urine, fèces, etc.) les éléments plus importants du système de régulation de la calcémie (calcium, phosphate, PTH et le calcitriol) et les administrer en expérimentes aigus. Cette possibilité est visible dans la littérature publiée dans ce domaine qui est en croissance permanente. L’avenir des techniques de biologie moléculaire a permis caractériser des nombreuses dysfonctions de la régulation de la calcémie et on attend un diagnostique physiopathologique de ces dysfonctions chaque fois plus rigoureuses. Les connaissances dans ce domaine s’agrandissent et on a de plus de capacités pour faire des diagnostiques et il est chaque fois plus difficile les interpréter. L’analyse ou synthèse de systèmes complexes est l’activité plus noble des ingénieurs qui les permit dessiner des ponts, bateaux, avions ou automobiles. Avec des ordinateurs de médium ou grand port il les est possible utiliser descriptions mathématiques pour dessiner les systèmes et interpréter des éventuelles fautes d’opération. Ces descriptions mathématiques sont une séquence d’opérations réalisées dans un ordinateur selon « un programme informatique » qui ont reçu la désignation générique de modèles, pour analogie avec les équations de la physique qui ont été déduits d’un nombre de postulées et qu’ont permit représenter des processus physiques en équations mathématiques. Les fameuses équations de Newton sont peut-être les exemples plus connus des systèmes physiques. L’introduction des modèles mathématiques en biologie et en particulier en médecine est un évènement récent. Dans ce travaille, on a construit un modèle simplifié de l’homéostasie du calcium pour calculer les variables observables (concentrations de calcium, phosphate, PTH et calcitriol) pour les comparer. Les choix des components a été déterminés par notre expérience clinique et par l’information physiopathologique et clinique publiée. Le modèle a été construit de façon modulaire ce que permit leur postérieur expansion sans des grandes altérations dans la description mathématique et informatique déjà existante. Dans cette forme le modèle ne peut être utilisé comme un instrument de diagnostique. Il est un outil pour éclairer la physiopathologie. Le modèle a été utilisé pour simuler un certain nombre d’observations publiées et pour exemplifier leur possible utilisation clinique dans la simulation des hypothèses et de la physiopathologie des situations d’hypo ou hypercalcémie. On a fait une analyse des éléments des procès cliniques des malades observées dans le Service d’Endocrinologie de l’IPOFG-CROL, SA. Dans une population de 894 malades avec des différentes pathologies les valeurs de calcémie on une distribution uni modale avec une Médie de 9.56 mg/dL et une erreur standard de 0.41 mg/dL. Ces observations suggèrent que la calcémie soit sujette de régulation. En utilisant des résultats de travaux publiés dans lesquels le métabolisme du calcium a été changé par des infusions de calcium, calcitriol ou PTH, des études biochimiques et physiologiques sur des mécanismes d’action des éléments contrôleurs de la calcémie et de l’étude du comportement des organes cible (parathyroïdes, intestin, rein, os), il a été possible de construire un modèle mathématique de paramètres concentrés du système de régulation de la calcémie. Les expressions analytiques utilisées ont été basées sur la cinétique enzymatique de façon à que les paramètres aient eu une signification physique ou biologique. Le modèle est stable quand il n’est pas perturbé et transit entre états stationnaires quand il est sujet a des perturbations. A ce moment il fait des simulations qui reproduisent de façon satisfaisant un nombre d’observations expérimentales. La construction du modèle permit l’addiction de nouvelles relations dans les cas ou il est insuffisant. L’utilisation exhaustive du modèle a permit expliciter des aspects du métabolisme du calcium qui y ne sont pas compris – l’hyperplasie ou la formation des adénomes des parathyroïdes, les altérations de la structure des os, la participation d’outres éléments régulateurs (magnésium), ou sont insuffisamment décrites – les altérations du métabolisme des phosphates dans l’hypoparathyroidism. L’analyse de l’information des malades du Service d’Endocrinologie a permit caractériser les pathologies représentées et leurs possibles mécanismes physiopathologiques. Ces observations sont le point de départ pour les analyses futures. Sont des exemples des relations trouvées: la distribution des malades par deux groupes: ceux dans lequel la calcémie est déterminée par la PTH ou ceux dans lesquels la PTH est déterminée par la calcémie; la distribution sazonale de la concentration de la vitamine D; la corrélation négative entre la vitamine D et la PTH. On a eu la possibilité de déduire la cinétique de control de la PTH sur la synthèse du calcitriol. L’étude des niveaux circulants de PTH sur des sujets parathyroidectomisées a permit déduire leur taux de dégradation métabolique. Le modèle a permit simuler les relations Ca/PTH dans le sang, Ca/fraction éliminée par le rein, Ca/P dans le sang pour des valeurs normales ou hautes de calcium. On a fait des simulations de situations physiopathologiques (dans “malades virtuelles”): Infusions chroniques de calcium, PTH ou calcitriol; altérations des récepteurs. Ces simulations ne peuvent pas être réalisées dans les humains. Sont des exemples d’utilisation du modèle dans l’exploration des possibles mécanismes de la physiopathologie en observant des résultats quantitatifs inaccessibles à l’intuition. Le modèle a été utile pendant deux étapes des travaux: La première, dans sa construction on a choisi l’information disponible, son analyse quantitative, l’explicitation rigoureuse (analytique) des relations fonctionnelles entre les contrôleurs et les variables et sa intégration dans une structure globale. La deuxième, la simulation de situations expérimentales ou cliniques (du Service d’Endocrinologie) a obligé d’expliciter des raisonnements physiopathologiques généralement formulés utilisant l’intuition. Cette pratique a montré des comportements – action réduite des infusions de PTH (jusqu’à l’inhibition totale de leur respective sécrétion), nécessité d’augmenter la masse sécréteuse de la parathyroïde dans les insuffisants rénales, etc. La synthèse et utilisation du modèle n’ont pas besoin d’une formation avancée en mathématique et sont possibles grâce à un programme interactif qui a été conçu pour la simulation des systèmes dynamiques dans lesquels le programme se construit en anglais en utilisant la symbolique élémentaire de l’algèbre. La fonction noble de ces modèles est semblable à celles des physiques du XVII siècle: Permettre établir explications générales en fonctionnant comme un outil intellectuel pour manipuler des concepts et pour la réalisation d’expérimentes pensées en respectant certains principes de la physique (principe de la conservation) qu’établissent les frontières de la réalité.

Notes sur la géologie et la paléontologie du Miocène de Lisbonne. XXI Primeira caracterização de dinoflagelados dos níveis mais baixos da série miocénica de Lisboa

This is the first report on Dinoflagellata from lowermost Miocene beds in Portugal (Tagus basin, Lisbon region, exposure at Benfica). Some general data about Dinoflagellata are presented. Descriptions are provided for some forms: Gonyaulacysta tenuitabulata, Spiniferites ramosus, Achomosphaera sp., Hystrichokolpoma rigaudae, Homotriblium cf. pallidum, Cordosphaeridium sp, and Lingulodinium machaerophorum. Lithostratigraphical study of an important section along Circular highway at Benfica has shown that there is a hitherto unknown sedimentary cycle in Lisbon's lowermost Miocene (upper Oligocene?). Pollen and Ostracoda point out to an Lower Aquitanian or even Upper Chattian age for the first Neogene marine transgression in Portugal, previously considered as Upper Aquitanian or Lower Burdigalian.

Notes sur la géologie et la paleontology du Miocène de Lisbonne. XXII - Une Espèce nouvelle Pokornyella Lusitanica (Ostrocoda), dans le Miocène Inférieur du bassin du Tage

A new species, Pokornyella lusitanica (Ostracoda), from the Lower Miocene (Aquitanian) of the Lisbon area, is described. Some palaeoecological data are presented.

Faunes ichthyologiques du Néogène Supérieur d’Angola, leur âge, remarques sur le Pliocène marin en Afrique Australe

This note is concerned with fish remains from Upper Neogene beds at Farol das Lagostas (and nearby quarry of SECIL) and Baía Farta, mainly recovered by the author in 1960, 1961, 1963 and 1967. For further data see ANTUNES, 1964, pp. 213-215. All the forms identified until now (many of them for the first time) are show in «tableau I». Smaller ones are poorly represented. I. benedeni is provisorily accepted as a distinct species, though it may correspond to a dental morphotype that does exist equally in the extant I. oxyrhinchus (see text): therefore I. benedeni from Farol das Lagostas may after all represent only some dental variations that really belong in the form described as I. cf. oxyrhinchus. The presence of Aprionodon and Hypoprion could not be ascertained: Procarcharodon megalodon, Carcharodon carcharias, Isurus benedeni. Galeocerdo cuvieri, and Carcharhinus sp. I and sp. II are specially discussed. The whole fauna does not correspond either to a very shallow and coastal environment, or to deep waters far away from the coast. It clearly points out to warm waters: an acceptable model would be the fauna from the tropical Atlantic between Northern Angola and Senegal-Cape Verde. The age of this fauna was long regarded as Burdigalian. The data formerly presented (ANTUNES, 1963) that allowed us to ascribe a pliocene age to the uppermost Neogene beds of Farol das Lagostas (Neogene III, ANTUNES, 1964) are reviewed and developed in this paper. This view is corroborated by planctonic foraminifera and stratigraphical data which provide further evidence to prove the presence of miocene beds much younger than Burdigalian, and that some deposits previously correlated to this stage have instead a Plio-Pleistocene age. Fish fauna from Farol das Lagostas is very characteristic, with giant P. megalodon in association with C. carcharias (which predominates, and whose stratigraphical distribution is particularly discussed), and with other very advanced forms like the extant tiger shark, G. cuvieri, enormous I. Benedeni, Hemipristis, and Carcharhinus (whose size largely exceeds the maximum observed with miocene material). With the exception of P. megalodon (extinct) all the other forms show very close affinities, or even identity with modern species. Comparisons with very similar faunas from some South African localities that may also have a Pliocene age are also presented.

Contributions à la paleontology du Miocène moyen continental du basin du tage

This study on middle Miocene Charophytes from the Tagus'basin indicates the presence of two species. hitherto undescribed from these strata in Portugal, Correlation diagrams of height and width of gyrogonite demonstrate that the populations of Nitellopsis (Tectochara) etrusca from the localities Póvoa de Santarém and Pêro Filho are identical to that from La Grenatière (Hérault, France), The population of Lychnothamnus duplicicarinatus from Tremês is identical to that already known from Anwill (Switzerland). The age of this flora is therefore suggested as being the upper part of the middle Miocene. The results of Charophyte studies are in accordance with stratigraphical conclusions from previously conducted mammalian studies (Antunes and Mein), A table showing the distribution of species in the three portuguese localities is given.

Contributions à la paleontology du Miocène moyen continental du basin du tage

The lignite-clays of Póvoa de Santarém dated as Upper «Vindobonian» (mammalian zone MN6), fielded abundant remains of animals and plants (spores, pollens, seeds, etc.). The forms identified are indicative of several environments. Plants, either aquatic or belonging to swampy areas are predominant (Nuphar sp., Sparganium sp., Stratiotes kaltennordheimensis, cf. Ranunculus sp.). There are also remains of plants characteristiques of a humid rather than a swampy soil such as Polypodiaceae, Myrica ceriferiformis, Toddalia maii, Spirematospermum wetzeleri. The genera Vitis and Ephedra, although rare, point fowards the existence of drier regions in the neighbourhood. The presence of polens such as Picea indicate the presence at some distance less warm upland forest areas.

Les Hipparion du Portugal

This paper is concerned with Hipparion from Ribatejo, Portugal, and with the stratigraphy of the Neogene series of this region. The first two chapters are an introduction and an historical review. Paleontological study includes both a revision of the specimens accounted by ROMAN (1907) and the description of new material. Two forms were recognized, an early H. cf. primigenium, lower Vallesian in age, NM 9 mammal unit (from Archino, Vila Nova da Rainha, Aveiras de Cima), and a more advanced H. primigenium cf. melendezi. Upper Vallesian, NM 10 (possibly lowermost Turolian, NM 11) (at Azambujeira and Marmeleira). A synthesis of Middle and Upper Miocene from Ribatejo is also presented. Levels with H. p. cf. melendezi are somewhat older than «Upper Pontian», as it was previously acknowledged, they attain at the best the lowermost Turolian (approximately corresponding to «Upper Pontian»). Even higher levels may be Turolian in age, though they are not yet accurately dated. Almost all the localities are shown (tableau 11) according to its stratigraphical position; age, correspondance to mammal units from NM 5 to NM 10 (and may be also from NM 11 to NM 12), and correlation with marine formations near Lisbon are also taken in account. The stratigraphical position of localities such as Póvoa de Santarém, Quinta do Marmelal, Pero Filho, Azambujeira (lower levels), and Fonte do Pinheiro was revised; the stratigraphical position of Marmeleira was ascertained. The localities so far known correspond to NM 5 (?), NM 6, NM 8, NM 9, NM 10 and possibly to NM II and NM 12. A new interpretation (M. T. ANTUNES) of localities with oysters from Ribatejo allows a better correlation with vertebrate localities. Relationships with Serravallian transgression seem well established. Only two localities, Vila Nova da Rainha and Foz do Alviela, may possibly be correlated to V-b division of Lisbon (Langhian) with «Hispanotherium fauna». All the other localities are younger than Serravallian oyster beds. Undirect correlation shows that NM 6 localities are somewhat younger than the apogee ef Serravallian transgression (corresponding approximately to Blow's N 11 to N 13 zones based on planctonic foraminifera).

Contribution à l’étude du nannoplacton du leg 12, «sites» 118-119 (Ocean Atlantique)

This paper reports a Scanning Electron Microscopy study of some samples from the leg 12, Deep Sea Drilling Project, sites 118 and 119. The chronostratigraphic distribution, the frequency of the species identified and the datation of the samples studied are presented. In accordance with the calcareous nannofossil zonation proposed by E. MARTINI (1971) the samples from site 118 are ascribed to the Upper Miocene while the samples from site 119 are located between the Lower (NN1) and the Upper Miocene (NN10).

Notes sur la géologie et la paleontology du Miocène de Lisbonne

This note deals with the stratigraphical and paleontological study of the Palença section on the southern bank of the river Tagus, Portugal, and specially with its coccolithophorids. Three main lithostratigraphical units may be recognized: the lowest one does correspond to the upper part of COTTER's division II, the intermediate one to divisions III and IV-a, the third corresponding to pratically the whole division IV-b, However other and higher levels are also represented. Higher beds are also represented in the same sections; they are less well exposed and were not studied in detail. Caracterisation of biozones on the basis of Coccoliths so far found at Palença section is difficultsince MARTINI's zones have been defined mainly by forms of Discoaster and other genera that are wanting. However we can recognize that the richest assemblage (from beds 17-18, the uppermost layers of blue clays IV-a) may correspond to NN4. This is not in opposition to the results of the study of planctonic foraminifera, that are characteristic of BLOW's N7. Coccoliths from lower beds do not allow at present any valid comparisons.

Contributions à la Paléontologie du Miocène moyen continental du Bassin du Tage. I - Quelques mollusques - Pero Filho, Póvoa de Santarém, Sítio do Mirante

Some land and freshwater mollusks (Gastropoda, Pelecypoda) from three middle Miocene localities: Pêro Filho, Póvoa de Santarém, Sítio do Mirante, all in Ribatejo province, Portugal, are summarily studied. On a systematical viewpoint it has been shown (see also Tableau): - the presence of the genus Janulus, whose species only survive now at Madeira and Canary's islands; - the presence of "Helix" cotteri that may indeed belong in the genus Megalotachea, common in western Europe since "Helvetian" to Messinian times; - Limax, Testacella, Acroloxus and Pseudamnicola are quoted for the first time in portuguese tertiary formations; Ferrisia has been identified for the first time in Iberian Peninsule; - the presence of other forms previously quoted by ANTUNES & ZBYSZEWSKI (1973), is confirmed: Bithynia, Theodoxus, Pisidium. Such faunules are compatible with a middle Miocene age. On a paleobiogeographical viewpoint, some forms suggest mediterranean affinities. Fossil associations do correspond ecologically to either palustrine or stagnant, calm and shallow water conditions (Sítio do Mirante, and essentially also Póvoa de Santarém), or to fluviatile conditions (Pêro Filho).

Contributions à la Paléontologie du Miocène moyen continental du Bassin du Tage. II - Observations sur les dents pharyngiennes de poissons cyprinidés - Póvoa de Santarém.

The study of Cyprinid fish pharyngeal teeth, collected by M. Telles Antunes in continental "Helvetian" sediments from Póvoa de Santarém, makes possible to demonstrate the occurrence of two distinct species. One remains undetermined. The other belongs to the recent genus Leuciscus CUV. Several dental types of this genus are described and figured as Leuciscus antunesi nov. sp. Palaeoclimatical and palaeoecological interpretations are proposed.

Contributions à la Paléontologie du Miocène moyen continental du Bassin du Tage. III - Mammifères - Póvoa de Santarém, Pêro Filho et Chões (Secorio). Conclusions générales

This study on middle Miocene mammalian faunas from Tagus'basin deals particularly with some small mammals hitherto undescribed from Portugal, including a new Glirid (Paraglirulus scalabicensis nov. sp.); it allows an accurate datation by biostratigraphical standards, Megacricetodon crusafonti, Fahlbuschia darocensis, Cricetodon jotae being characteristic of mammalian MN6 unit, thus their age is nearly that of Sansan and Manchones (however the presence of Peridyromys hamadryas and Lagopsis verus do suggest, amidst this biozone, a somewhat later age than Sansan's); it contributes with indirect correlation data with marine formations, as underlying oyster-bearing beds most probably are in correspondance to the apogee of the same transgression that deposed near Lisbon ”schlier" facies from VI-a division (Serravalian, Blow's zones 10-13, Globorotalia meyeri zone); the diversity of mammalian assemblages is surely related to an environement with varied biotopes, whose characterisation becomes easier if account is taken of the preceding papers on mollusks (G. Truc) and Cyprinid fishes (J. Gaudant), and also according to some unpublished paleobotanical data (J. Pais). A table with a synthesis of all paleontological data so far known is presented.

Cheirogaster sp. (O. Testudines, Fam. Testudinidae, Geochelone sl.) du Paléogène de Naia, Tondela et l’âge du gisement

A land tortoise from a new locality at Naia, Tondela, is described. It is to be reported either to an advanced form of the genus Hadrianus or to an archaic representative of Cheirogaster; it may be included in the comprehensive genus Geochelone s.l., excluding however Ergilemys and its descendants. There is a strong possibility in favour of Cheirogaster. Testudo must also be excluded. It is not possible to classify this specimen at species'level. Our specimen does agree best with Upper Eocene Testudinidae and with some Lower Oligocene ones. Its age is certainly not Upper Oligocene or later, nor Lower and Middle Eocene. This datation is not opposed to the age of the fossiliferous clays of Naia as supposed by correlation with another locality - Côja, about 30 km to the South - which yielded an assemblage of mammals whose Ludian (Upper Bartonian s.l.) age seems well established. Naia and Côja's fossil-bearing clays must be nearly synchronous; their origin is well in place among the phenomena related to the surrection of iberian Central Chain during paroxysmal phase of pyrenean orogenesis.

Connaissances stratigraphiques sur la base du Mésozoique portugais

In Portugal, the Mesozoic lower part is principally composed of conglomeratic, arenitic and pelitic deposits, which are here and there associated with carbonates rocks and evaporites. The Germanic Triassic succession is not observed. The Muschelkalk facies do not exist. Carbonates formation, and some thick evaporites deposits (Keuper facies) are of early Jurassic in age. The thick red beds accumulations deposited in a continental environment are Triassic. In Coimbra area the oldest palynomorphs found are Camian-Norian. In South Portugal (Algarve), the triassic serie must be more complete with a lower Triassic rich in Stegocephales bone-beds.

Faciès, biostratigraphie et paléogéographie du Jurassique portugais

The facies distribution along the Jurassic stages in an already well established stratigraphic frame is defined for the three portuguese basins: North of Tagus, Santiago de Cacém and Algarve. The deposits are organized in two sedimentary cycles. The first one from the Liassic to Calovian shows, in the Tagus Basin, a transgression from NW which did not surpass the Meseta present limits. The iniatilly brackish deposits only changed to marine by the end of Lotharingian. The sedimentation, mainly marly during the Liassic became more calcareous since the Aalenian. During the Dogger the basin differentiated into platform deposits towards East and South and open sea zone towards West. This zone underwent a progressive reduction and, during the Callovian, two small basins were individualized: Cabo Mondego basin in the North and Serra de El-Rei-Montejunto in the South. It is from the latter that the second sedimentary cycle (Middle Oxfordian-Portlandian) developed with open sea deposits along the Sintra–Torres Vedras axis surrounded by platform and litoral brackish formations. During the first sedimentary cycle only litoral platform deposits are known in Santiago de Cacém and Algarve basins. During the second sedimentary cycle temporary sea open deposits are known in Santiago de Cacém and Central Algarve.